Required Text

Buy at Amazon Lodish, Harvey, Matthew P. Scott, Paul Matsudaira, James Darnell, Lawrence Zipursky, Chris A. Kaiser, Arnold Berk, and Monty Krieger. Molecular Cell Biology. New York, NY: W.H. Freeman, 2003. ISBN: 9780716743668.

Readings by Session

1 Introduction - Quantitative/Integrative Systems Approach to Biology  
2 Genomics Technologies - Sequencing Drmanac, R., S. Drmanac, G. Chui, R. Diaz, A. Hou, H. Jin, P. Jin, S. Kwon, S. Lacy, B. Moeur, J. Shafto, D. Swanson, T. Ukrainczyk, C. Xu, and D. Little. "Sequencing by hybridization (SBH): advantages, achievements, and opportunities." Adv Biochem Eng Biotechnol 77 (2002): 75-101.

Graves, D. J. "Powerful tools for genetic analysis come of age." Trends Biotechnol 17, no. 3 (March 1999): 127-34.

Shendure, J., R. D. Mitra, C. Varma, and G. M Church. "Advanced sequencing technologies: methods and goals." Nat Rev Genet 5, no. 5 (May 2004): 335-44.
3 Genomics Technologies - Gene Expression Lipshutz, R. J., S. P. Fodor, T. R. Gingeras, and D. J. Lockhart. "High density synthetic oligonucleotide arrays." Nat Genet 21, no. 1 (January 1999): 20-4. (Supplementary)

Schulze, A., and J. Downward. "Navigating gene expression using microarrays-a technology review." Nat Cell Biol 3, no. 8 (August 2001): E190-5.

Wong, M. L., and J. F. Medrano. "Real-time PCR for mRNA quantitation." Biotechniques 39, no. 1 (July 2005): 75-85.
4 Genomics Technologies - Computational Analysis Baldwin, D. N., V. Vanchinathan, P. O. Brown, and J. A. Theriot. "A gene-expression program reflecting the innate immune response of cultured intestinal epithelial cells to infection by Listeria monocytogenes." Genome Biol 4, no. 1 (2003): R2; Epub (December 23, 2002).

Kuruvilla, F. G., P. J. Park, and S. L. Schreiber. "Vector algebra in the analysis of genome-wide expression data." Genome Biol 3, no. 3 (2002): RESEARCH0011; Epub (February 13, 2002).

Sherlock, G. "Analysis of large-scale gene expression data." Curr Opin Immunol 12, no. 2 (April 2000): 201-5.
5 Genes and Disease - Analysis and Statistics I Morgenthaler, Stephan, and William G. Thilly. "A strategy to discover genes that carry multi-allelic and multigenic risk for common diseases: a cohort allelic sums test (CAST)." Submitted to Mutation Research (January 20, 2006).
6 Genes and Disease - Analysis and Statistics II  
7 Genomics and Gene Expression - Pathophysiological Applications Haugen, A. C., R. Kelley, J. B. Collins, C. J. Tucker, C. Deng, C. A. Afshari, J. M. Brown, T. Ideker, and B. Van Houten. "Integrating phenotypic and expression profiles to map arsenic-response networks." Genome Biol 5, no. 12 (2004): R95; Epub (November 29, 2004).

Huang, C., Q. Ke, M. Costa, and X. Shi. "Molecular mechanisms of arsenic carcinogenesis." Mol Cell Biochem 255, no. 1-2 (January 2004): 57-66.

Kitchin, K. T. "Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites." Toxicol Appl Pharmacol 172, no. 3 (May 1, 2001): 249-61.

Rossman, T. G. "Mechanism of arsenic carcinogenesis: an integrated approach." Mutat Res 533, no. 1-2 (December 10, 2003): 37-65.

Chou, W. C., C. Jie, A. A. Kenedy, R. J. Jones, M. A. Trush, and C. V. Dang. "Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells." Proc Natl Acad Sci USA 101, no. 13 (March 30, 2004): 4578-83; Epub (March 15, 2004).
8 Genomics to Proteomics - mRNA to Protein Relationships White, S. L., S. Gharbi, M. F. Bertani, H. L. Chan, M. D. Waterfield, and J. F. Timms. "Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression." Br J Cancer 90, no. 1 (January 12, 2004): 173-81.

Cox, B., T. Kislinger, and A. Emili. "Integrating gene and protein expression data: pattern analysis and profile mining." Methods 35, no. 3 (March 2005): 303-14; Epub (January 12, 2005).
9 Proteins and Proteomics - Flow Cytometry Approaches Krutzik, P. O., J. M. Irish, G. P. Nolan, and O. D. Perez. "Analysis of protein phosphorylation and cellular signaling events by flow cytometry: techniques and clinical applications." Clin Immunol 110, no. 3 (March 2004): 206-21.

Perez, O. D., D. Mitchell, G. C. Jager, S. South, C. Murriel, J. McBride, L. A. Herzenberg, S. Kinoshita, and G. P. Nolan. "Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1." Nat Immunol 4, no. 11 (November 2003): 1083-92; Epub (October 5, 2003).
10 Proteins and Proteomics - Protein Network Dynamics Sachs, K., O. Perez, D. Pe'er, D. A. Lauffenburger, and G. P. Nolan. "Causal protein-signaling networks derived from multiparameter single-cell data." Science 308, no. 5721 (April 22, 2005): 523-9.

Eddy, S. R. "What is Bayesian statistics?" Nat Biotechnol 22, no. 9 (September 2004): 1177-8.

Online tutorial on Bayesian networks.
11 Proteins and Proteomics - Arrays and Gels Sitek, B., O. Apostolov, K. Stuhler, K. Pfeiffer, H. E. Meyer, A. Eggert, and A. Schramm. "Identification of dynamic proteome changes upon ligand activation of Trk-receptors using two-dimensional fluorescence difference gel electrophoresis and mass spectrometry." Mol Cell Proteomics 4, no. 3 (March 2005): 291-9; Epub (January 15, 2005).

Ptacek, J., G. Devgan, G. Michaud, H. Zhu, X. Zhu, J. Fasolo, H. Guo, G. Jona, A. Breitkreutz, R. Sopko, R. R. McCartney, M. C. Schmidt, N. Rachidi, S. J. Lee, A. S. Mah, L. Meng, M. J. Stark, D. F. Stern, C. De Virgilio, M. Tyers, B. Andrews, M. Gerstein, B. Schweitzer, P. F. Predki, and M. Snyder. "Global analysis of protein phosphorylation in yeast." Nature 438, no. 7068 (December 1, 2005): 679-84.

Somiari, R. I., A. Sullivan, S. Russell, S. Somiari, H. Hu, R. Jordan, A. George, R. Katenhusen, A. Buchowiecka, C. Arciero, H. Brzeski, J. Hooke, and C. Shriver. "High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast." Proteomics 3, no. 10 (October 2003): 1863-73.

Kolkman, A., E. H. Dirksen, M. Slijper, and A. J. Heck. "Double standards in quantitative proteomics: direct comparative assessment of difference in gel electrophoresis and metabolic stable isotope labeling." Mol Cell Proteomics 4, no. 3 (March 2005): 255-66; Epub (January 4, 2005).

Patton, W. F. "A thousand points of light: the application of fluorescence detection technologies to two-dimensional gel electrophoresis and proteomics." Electrophoresis 21, no. 6 (April 2000): 1123-44.
12 Proteins and Proteomics - Mass Spectrometry Approaches Glish, G. L., R. W. Vachet. "The basics of mass spectrometry in the twenty-first century." Nat Rev Drug Discov 2, no. 2 (February 2003): 140-50.

Bhat, V. B., M. H. Choi, J. S. Wishnok, and S. R. Tannenbaum. "Comparative plasma proteome analysis of lymphoma-bearing SJL mice." J Proteome Res 4, no. 5 (September-October, 2005): 1814-25.

Mass spec website on peptide fragmentation.
13 Proteins and Proteomics - Protein Network Topologies Hoffmann, A., A. Levchenko, M. L. Scott, and D. Baltimore. "The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation." Science 298, no. 5596 (November 8, 2002): 1241-5.

Aggarwal, B. B. "Nuclear factor-kappaB: the enemy within." Cancer Cell 6, no. 3 (September 2004): 203-8.

Ting, A. Y., and D. Endy. "Signal transduction. Decoding NF-kappaB signaling." Science 298, no. 5596 (November 8, 2002): 1189-90.
14 Project Planning Presentations  
15 Project Planning Presentations (cont.)  
16 Tissues and Animals - Technologies for Cellular Analysis Saghatelian, A., and B. F. Cravatt. "Global strategies to integrate the proteome and metabolome." Curr Opin Chem Biol 9, no. 1 (February 2005): 62-8.

Saghatelian, A., S. A. Trauger, E. J. Want, E. G. Hawkins, G. Siuzdak, and B. F. Cravatt. "Assignment of endogenous substrates to enzymes by global metabolite profiling." Biochemistry 43, no. 45 (November 16, 2004): 14332-9.
17 Tissues and Animals - Pathophysiological Application Nicholson, J. K., J. Connelly, J. C. Lindon, and E. Holmes. "Metabonomics: a platform for studying drug toxicity and gene function." Nat Rev Drug Discov 1, no. 2 (February 2002): 153-61.

Mortishire-Smith, R. J., G. L. Skiles, J. W. Lawrence, S. Spence, A. W. Nicholls, B. A. Johnson, and J. K. Nicholson. "Use of metabonomics to identify impaired fatty acid metabolism as the mechanism of a drug-induced toxicity." Chem Res Toxicol 17, no. 2 (February 2004): 165-73.

Lindon, J. C., E. Holmes, and J. K. Nicholson. "So what's the deal with metabonomics?" Anal Chem 75, no. 17 (September 1, 2003): 384A-391A.
18 Ethics and Responsible Conduct of Research Ethics questions (PDF)

Martinson, B. C., M. S. Anderson, and R. de Vries. "Scientists behaving badly." Nature 435, no. 7043 (June 9, 2005): 737-8.

Grinnell, F. "Misconduct: acceptable practices differ by field." Nature 436, no. 7052 (August 11, 2005): 776.

Taylor, I. "Academia's 'misconduct' is acceptable to industry." Nature 436, no. 7051 (August 4, 2005): 626.

Clouthier, S. G. "Misconduct: lower ranks take most of the blame." Nature 436, 7050 (July 28, 2005): 460.

Wadman, M. "One in three scientists confesses to having sinned." Nature 435, no. 7043 (June 9, 2005): 718-9.

Deichmann, U., and B. Muller-Hill. "The fraud of Abderhalden's enzymes." Nature 393, no. 6681 (May 14, 1998): 109-11.
19 Ethics and Responsible Conduct of Research (cont.) Bonetta, Laura, ed. "Mentoring and Being Mentored." Chapter 5 in Making the Right Moves: A Practical Guide to Scientific Management for Postdocs and New Faculty. Chevy Chase, Maryland: Howard Hughes Medical Institute and Research; Triangle Park, North Carolina: Burroughs Wellcome Fund, 2004.

Editors of the Publications Division of the American Chemical Society. "Ethical Guidelines to Publication of Chemical Research." American Chemical Society (January, 2000).

Important Questions for Collaborations. Template developed by the NIH Ombudsman for establishing collaborations.

Publication practices, authorship, peer-review, and collaborations. NIH Web site on Ethical Conduct.
20 Tissues and Animals - Transgenic Animal Models Branda, C. S., and S. M. Dymecki. "Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice." Dev Cell 6, no. 1 (January 2004): 7-28.

Andreu, P., S. Colnot, C. Godard, S. Gad, P. Chafey, M. Niwa-Kawakita, P. Laurent-Puig, A. Kahn, S. Robine, C. Perret, and B. Romagnolo. "Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine." Development 132, no. 6 (March 2005): 1443-51; Epub (February 16, 2005).

Kucherlapati, M. H., A. A. Nguyen, R. T. Bronson, and R. S. Kucherlapati. "Inactivation of conditional Rb by Villin-Cre leads to aggressive tumors outside the gastrointestinal tract." Cancer Res 66, no. 7 (April 1, 2006): 3576-83.
21 Tissues and Animals - Metabolomics Gillespie, J. W., G. Gannot, M. A. Tangrea, M. Ahram, C. J. Best, V. E. Bichsel, E. F. Petricoin, M. R. Emmert-Buck, and R. F. Chuaqui. "Molecular profiling of cancer." Toxicol Pathol 32, no. 1 (March-April, 2004): 67-71. (Supplement)

Kunz, G. M., Jr., and D. W. Chan. "The use of laser capture microscopy in proteomics research-a review." Dis Markers 20, no. 3 (2004): 155-60.

Petricoin, E. F., K. C. Zoon, E. C. Kohn, J. C. Barrett, and L. A. Liotta. "Clinical proteomics: translating benchside promise into bedside reality." Nat Rev Drug Discov 1, no. 9 (September 2002): 683-95.

Paweletz, C. P., L. Charboneau, V. E. Bichsel, N. L. Simone, T. Chen, J. W. Gillespie, M. R. Emmert-Buck, M. J. Roth, E. F. Petricoin, III, and L. A. Liotta. "Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front." Oncogene 20, no. 16 (April 12, 2001): 1981-9.
22 Tissues and Animals - Tissue Engineering Models Sivaraman, A., J. K. Leach, S. Townsend, T. Iida, B. J. Hogan, D. B. Stolz, R. Fry, L. D. Samson, S. R. Tannenbaum, L. G. Griffith. "A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction." Curr Drug Metab 6, no. 6 (December 2005): 569-91.

Griffith, L. G., and M. A. Swartz. "Capturing complex 3D tissue physiology in vitro." Nat Rev Mol Cell Biol 7, no. 3 (March 2006): 211-24.
23-26 Project Presentations